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Equilibrium protein folding-unfolding process involving multiple intermediates

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Abstract

Mathematical models for the protein folding-unfolding process involving multiple intermediates have been derived. Computer fitting of the experimental data to this model generates various thermodynamic parameters for the folding-unfolding process. In this way, the complex folding-unfolding process of the multi-domain proteins can be analysed in a quantitative way. The application of the folding-unfolding model involving seven stages in human placental alkaline phosphatase is described.

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References

  • Bai, Y. and S. W. Englander (1996). Future directions in folding: the multi-state nature of protein structure. Proteins 24, 145–151.

    Article  Google Scholar 

  • Dignam, J. D., X. Qu and J. B. Chaires (2001). Equilibrium unfolding of Bombyx mori glycyl-tRNA synthetase. J. Biol. Chem. 276, 4028–4037.

    Article  Google Scholar 

  • Dobryszycki, P., M. Rymarczuk, G. Bulaj and M. Kochman (1999). Effect of acrylamide on aldolase structure. I. Induction of intermediate states. Biochim. Biophys. Acta 1431, 338–350.

    Google Scholar 

  • Ferreira, S. T. and F. G. De Felice (2001). Protein dynamics, folding and misfolding: from basic physical chemistry to human conformational diseases. FEBS Lett. 498, 129–134.

    Article  Google Scholar 

  • Fink, A. L., K. A. Oberg and S. Seshadri (1998). Discrete intermediates versus molten globule models for protein folding: characterization of partially folded intermediates of apomyoglobin. Fold. Des. 3, 19–25.

    Article  Google Scholar 

  • Herbst, R., K. Gast and R. Seckler (1998). Folding of firefly (Photinus pyralis) luciferase: aggregation and reactivation of unfolding intermediates. Biochemistry 37, 6586–6597.

    Article  Google Scholar 

  • Herbst, R., U. Schafer and R. Seckler (1997). Equilibrium intermediates in the reversible unfolding of firefly (Photinus pyralis) luciferase. J. Biol. Chem. 272, 7099–7105.

    Article  Google Scholar 

  • Hung, H. C. and G. G. Chang (1998). Biphasic denaturation of human placental alkaline phosphatase in guanidinium chloride. Proteins 33, 49–61.

    Article  Google Scholar 

  • Hung, H. C. and G. G. Chang (2001). Multiple unfolding intermediates of human placental alkaline phosphatase in the equilibrium urea denaturation. Biophys. J. 81, 3456–3471.

    Google Scholar 

  • Jaenicke, R. (1996). Protein folding and association: in vitro studies for self-organization and targeting in the cell. Curr. Top. Cell. Regul. 34, 209–314.

    Article  Google Scholar 

  • Jaenicke, R. (1999). Stability and folding of domain proteins. Prog. Biophys. Mol. Biol. 71, 155–241.

    Article  Google Scholar 

  • Lansbury, P. T. Jr (1999). Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc. Natl Acad. Sci. USA 96, 3342–3344.

    Article  Google Scholar 

  • Le Du, M. H., T. Stigbrand, M. J. Taussig, A. Ménez and E. A. Stura (2001). Crystal structure of alkaline phosphatase from human placenta at 1.8 Å resolution. Implication for a substrate specificity. J. Biol. Chem. 276, 9158–9165.

    Article  Google Scholar 

  • Lebowitz, J., M. S. Lewis and P. Schuck (2002). Modern analytical ultracentrifugation in protein science: a tutorial review. Protein Sci. 11, 2067–2079.

    Article  Google Scholar 

  • McComb, R. B., G. N. Bowers Jr and S. Posen (1979). Alkaline Phosphatase, New York, London: Plenum, pp. 189–287.

    Google Scholar 

  • Noland, B. W., L. J. Dangott and T. O. Baldwin (1999). Folding, stability, and physical properties of the alpha subunit of bacterial luciferase. Biochemistry 38, 16136–16145.

    Google Scholar 

  • Pace, C. N. (1990). Measuring and increasing protein stability. Trends Biotechnol. 8, 93–98.

    Article  Google Scholar 

  • Privalov, P. L. (1996). Intermediate states in protein folding. J. Mol. Biol. 258, 707–725.

    Article  Google Scholar 

  • Radford, S. E. (2000). Protein folding: progress made and promises ahead. Trends Biochem. Sci. 25, 611–618.

    Article  Google Scholar 

  • Santoro, M. M. and D. W. Bolen (1988). Unfolding free energy changes determined by the linear extrapolationmethod. 1. Unfolding of phenylmethanesulfonylα-chymotrypsin using different denaturants. Biochemistry 27, 8063–8068.

    Article  Google Scholar 

  • Schuck, P. (2000). Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling. Biophys. J. 78, 1606–1619.

    Article  Google Scholar 

  • Soto, C. (2001). Protein misfolding and disease; protein refolding and therapy. FEBS Lett. 498, 204–207.

    Article  Google Scholar 

  • Sussman, H. H. (1984). Structural analysis of human alkaline phosphatase, in Human Alkaline Phosphatase, T. Stigbrand and W. H. Fishman (Eds), New York: Alan R. Liss, pp. 87–103.

    Google Scholar 

  • Tsai, C. J., B. Ma, Y. Y. Sham, S. Kumar and R. Nussinov (2001). Structured disorder and conformational selection. Proteins 44, 418–427.

    Article  Google Scholar 

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Correspondence to Gu-Gang Chang.

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These authors contributed equally to this paper.

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Hung, HC., Chen, YH., Liu, GY. et al. Equilibrium protein folding-unfolding process involving multiple intermediates. Bull. Math. Biol. 65, 553–570 (2003). https://doi.org/10.1016/S0092-8240(03)00024-7

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  • DOI: https://doi.org/10.1016/S0092-8240(03)00024-7

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